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Addiction (Abingdon, England) Oct 2022There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of pharmacotherapies for AW.
METHODS
Six databases were searched for randomized clinical trials through November 2021. Trials were included after a blinded review by two independent reviewers. Outcomes included incident seizures, delirium tremens, AW severity scores, adverse events, dropouts, dropouts from adverse events, length of hospital stay, use of additional medications, total benzodiazepine requirements, and death. Effect sizes were pooled using frequentist random-effects network meta-analysis models to generate summary ORs and Cohen's d standardized mean differences (SMDs).
RESULTS
Across the 149 trials, there were 10 692 participants (76% male, median 43.5 years old). AW severity spanned mild (n = 32), moderate (n = 51), and severe (n = 66). Fixed-schedule chlormethiazole (OR, 0.16; 95% CI, 0.04-0.65), fixed-schedule diazepam (OR, 0.16; 95% CI, 0.04-0.59), fixed-schedule lorazepam (OR = 0.19; 95% CI, 0.08-0.45), fixed-schedule chlordiazepoxide (OR = 0.21; 95% CI, 0.08-0.53), and divalproex (OR = 0.22; 95% CI, 0.05-0.86) were superior to placebo at reducing incident AW seizures. However, only fixed-schedule diazepam (OR, 0.19; 95% CI, 0.05-0.76) reduced incident delirium tremens. Oxcarbazepine (d = -3.69; 95% CI, -6.21 to -1.17), carbamazepine (d = -2.76; 95% CI, -4.13 to -1.40), fixed-schedule oxazepam (d = -2.55; 95% CI, -4.26 to -0.83), and γ-hydroxybutyrate (d = -1.80; 95% CI, -3.35 to -0.26) improved endpoint Clinical Institute Withdrawal Assessment for Alcohol-Revised scores over placebo. Promazine and carbamazepine were the only agents significantly associated with greater dropouts because of adverse events. The quality of evidence was downgraded because of the substantial risk of bias, heterogeneity, inconsistency, and imprecision.
CONCLUSIONS
Although some pharmacotherapeutic modalities, particularly benzodiazepines, appear to be safe and efficacious for reducing some measures of alcohol withdrawal, methodological issues and a high risk of bias prevent a consistent estimate of their comparative performance.
Topics: Adult; Alcohol Withdrawal Delirium; Alcoholism; Benzodiazepines; Carbamazepine; Diazepam; Female; Humans; Male; Network Meta-Analysis; Seizures; Substance Withdrawal Syndrome
PubMed: 35194860
DOI: 10.1111/add.15853 -
The Cochrane Database of Systematic... Dec 2020Anxiety in relation to surgery is a well-known problem. Melatonin offers an alternative treatment to benzodiazepines for ameliorating this condition in the preoperative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anxiety in relation to surgery is a well-known problem. Melatonin offers an alternative treatment to benzodiazepines for ameliorating this condition in the preoperative and postoperative periods.
OBJECTIVES
To assess the effects of melatonin on preoperative and postoperative anxiety compared to placebo or benzodiazepines.
SEARCH METHODS
We searched the following databases on 10 July 2020: CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science. For ongoing trials and protocols, we searched clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform.
SELECTION CRITERIA
We included randomized, placebo-controlled or standard treatment-controlled (or both) studies that evaluated the effects of preoperatively administered melatonin on preoperative or postoperative anxiety. We included adult patients of both sexes (15 to 90 years of age) undergoing any kind of surgical procedure for which it was necessary to use general, regional, or topical anaesthesia.
DATA COLLECTION AND ANALYSIS
One review author conducted data extraction in duplicate. Data extracted included information about study design, country of origin, number of participants and demographic details, type of surgery, type of anaesthesia, intervention and dosing regimens, preoperative anxiety outcome measures, and postoperative anxiety outcome measures.
MAIN RESULTS
We included 27 randomized controlled trials (RCTs), involving 2319 participants, that assessed melatonin for treating preoperative anxiety, postoperative anxiety, or both. Twenty-four studies compared melatonin with placebo. Eleven studies compared melatonin to a benzodiazepine (seven studies with midazolam, three studies with alprazolam, and one study with oxazepam). Other comparators in a small number of studies were gabapentin, clonidine, and pregabalin. No studies were judged to be at low risk of bias for all domains. Most studies were judged to be at unclear risk of bias overall. Eight studies were judged to be at high risk of bias in one or more domain, and thus, to be at high risk of bias overall. Melatonin versus placebo Melatonin probably results in a reduction in preoperative anxiety measured by a visual analogue scale (VAS, 0 to 100 mm) compared to placebo (mean difference (MD) -11.69, 95% confidence interval (CI) -13.80 to -9.59; 18 studies, 1264 participants; moderate-certainty evidence), based on a meta-analysis of 18 studies. Melatonin may reduce immediate postoperative anxiety measured on a 0 to 100 mm VAS compared to placebo (MD -5.04, 95% CI -9.52 to -0.55; 7 studies, 524 participants; low-certainty evidence), and may reduce delayed postoperative anxiety measured six hours after surgery using the State-Trait Anxiety Inventory (STAI) (MD -5.31, 95% CI -8.78 to -1.84; 2 studies; 73 participants; low-certainty evidence). Melatonin versus benzodiazepines (midazolam and alprazolam) Melatonin probably results in little or no difference in preoperative anxiety measured on a 0 to 100 mm VAS (MD 0.78, 95% CI -2.02 to 3.58; 7 studies, 409 participants; moderate-certainty evidence) and there may be little or no difference in immediate postoperative anxiety (MD -2.12, 95% CI -4.61 to 0.36; 3 studies, 176 participants; low-certainty evidence). Adverse events Fourteen studies did not report on adverse events. Six studies specifically reported that no side effects were observed, and the remaining seven studies reported cases of nausea, sleepiness, dizziness, and headache; however, no serious adverse events were reported. Eleven studies measured psychomotor and cognitive function, or both, and in general, these studies found that benzodiazepines impaired psychomotor and cognitive function more than placebo and melatonin. Fourteen studies evaluated sedation and generally found that benzodiazepine caused the highest degree of sedation, but melatonin also showed sedative properties compared to placebo. Several studies did not report on adverse events; therefore, it is not possible to conclude with certainty, from the data on adverse effects collected in this review, that melatonin is better tolerated than benzodiazepines.
AUTHORS' CONCLUSIONS
When compared with placebo, melatonin given as premedication (as tablets or sublingually) probably reduces preoperative anxiety in adults (measured 50 to 120 minutes after administration), which is potentially clinically relevant. The effect of melatonin on postoperative anxiety compared to placebo (measured in the recovery room and six hours after surgery) was also evident but was much smaller, and the clinical relevance of this finding is uncertain. There was little or no difference in anxiety when melatonin was compared with benzodiazepines. Thus, melatonin may have a similar effect to benzodiazepines in reducing preoperative and postoperative anxiety in adults.
Topics: Adult; Aged; Aged, 80 and over; Alprazolam; Anti-Anxiety Agents; Anxiety; Bias; Clonidine; Drug Administration Schedule; Humans; Melatonin; Midazolam; Middle Aged; Oxazepam; Postoperative Care; Postoperative Complications; Preoperative Care; Publication Bias; Randomized Controlled Trials as Topic; Surgical Procedures, Operative
PubMed: 33319916
DOI: 10.1002/14651858.CD009861.pub3 -
The Cochrane Database of Systematic... Aug 2019Catatonia is a debilitating disorder of movement and volition associated with schizophrenia and some other mental illnesses. People with catatonia are more likely to...
BACKGROUND
Catatonia is a debilitating disorder of movement and volition associated with schizophrenia and some other mental illnesses. People with catatonia are more likely to require hospitalisation and highly supervised care than those without the disorder. They also have an increased risk of secondary complications such as pneumonia, malnutrition and dehydration. The mainstay of treatment has been drug therapies and electroconvulsive therapy.
OBJECTIVES
To compare the effects of benzodiazepines with other drugs, placebo or electroconvulsive therapy for catatonia in people with schizophrenia or other similar serious mental illnesses (SMIs).
SEARCH METHODS
We updated our previous search (28 February 2007) by searching the Cochrane Schizophrenia Group's Study-Based Register of Trials (9 November 2016; 6 February 2019). This register is compiled by systematic searches of major resources (including CENTRAL, MEDLINE, Embase, AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings, with no language, date, document type, or publication status limitations for inclusion of records into the register. We also manually searched reference lists from studies selected by the search.
SELECTION CRITERIA
All controlled clinical trials that randomised people who have schizophrenia or other similar SMI and experiencing catatonia to receive benzodiazepines or another relevant treatment. We included studies that met our inclusion criteria and reported usable data. We excluded those not meeting our inclusion criteria or those not reporting usable data. We contacted authors when we required further information; and if we received no response, we put those studies aside as 'awaiting assessment'.
DATA COLLECTION AND ANALYSIS
Review authors extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis using a fixed-effect model. We completed a 'Risk of bias' assessment for the included study and generated a 'Summary of findings' table using GRADE.
MAIN RESULTS
The searches found 130 citations, from which we could identify 22 possibly relevant studies. From these, we could only include one study. This study had a relatively small sample size of 17 participants who received lorazepam or oxazepam and were drug free for one week before the trial started. The only usable data reported by this study were clinically important change in symptoms of catatonia measured as 50% improvement on the Visual Analogue Scale (VAS). There was no difference in the numbers of participants showing a clinically important change in their catatonic symptoms (RR 0.95, 95% CI 0.42 to 2.16; participants = 17; studies = 1; very low quality evidence).No data were reported for other important outcomes of hospital stay, clinically important change in satisfaction with care, global state, adverse effects or general functioningWe did find a few studies meeting our inclusion criteria but they reported no usable data. We had to exclude these. Although poorly reported, these studies do illustrate that relevant studies have been undertaken - they are not impossible to design and conduct.
AUTHORS' CONCLUSIONS
Analysis of the results from this review, which was a head-to-head comparison of two benzodiazepine monotherapies, does not show a clear difference in effect. No data were available for benzodiazepines compared to placebo or standard care. The lack of usable data and very low quality of data available makes it impossible to draw firm conclusions and further studies with a high-quality methodology and reporting are required in order to determine more definitively the outcomes associated with benzodiazepine use in the clinical management of catatonia in persons with schizophrenia and other SMI.
Topics: Antipsychotic Agents; Benzodiazepines; Catatonia; Electroconvulsive Therapy; Humans; Mental Disorders; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenia, Catatonic
PubMed: 31425609
DOI: 10.1002/14651858.CD006570.pub3 -
The Journal of Laryngology and Otology Jul 2015To investigate the effectiveness of benzodiazepine use for subjective tinnitus and to consider this in the context of the concomitant side effects. (Review)
Review
OBJECTIVES
To investigate the effectiveness of benzodiazepine use for subjective tinnitus and to consider this in the context of the concomitant side effects.
METHODS
A systematic search of several databases using the terms 'tinnitus' and 'benzodiazepines' was conducted to find clinical trials of benzodiazepines and comparators in tinnitus patients. These studies were then assessed for risk of bias.
RESULTS
Six clinical trials were included. Clonazepam was found to be effective in three studies, but these studies had limitations regarding adequate blinding. The effectiveness of alprazolam was equivocal. Diazepam was not effective in two studies and oxazepam was effective in one study.
CONCLUSION
Benzodiazepine use for subjective tinnitus does not have a robust evidence base. Clonazepam has the most evidence to support its use and is relatively less likely to lead to abuse because of its longer half-life, but caution is still needed given the other serious side effects.
Topics: Benzodiazepines; GABA Modulators; Humans; Randomized Controlled Trials as Topic; Tinnitus; Treatment Outcome
PubMed: 25858126
DOI: 10.1017/S0022215115000808 -
American Journal of Alzheimer's Disease... Nov 2014The objective of this review is to summarize the available data on the use of benzodiazepines for the treatment of behavioral and psychological symptoms of dementia... (Review)
Review
The objective of this review is to summarize the available data on the use of benzodiazepines for the treatment of behavioral and psychological symptoms of dementia (BPSD) from randomized controlled trials (RCTs). A systematic search of 5 major databases, PubMed, MEDLINE, PsychINFO, EMBASE, and Cochrane Collaboration, yielded a total of 5 RCTs. One study compared diazepam to thioridazine, 1 trial compared oxazepam to haloperidol and diphenhydramine, 1 trial compared alprazolam to lorazepam, 1 trial compared lorazepam to haloperidol, and 1 trial compared intramuscular (IM) lorazepam to IM olanzapine and placebo. The data indicates that in 4 of the 5 studies, there was no significant difference in efficacy between the active drugs to treat the symptoms of BPSD. One study indicated that thioridazine may have better efficacy than diazepam for treating symptoms of BPSD. In 1 study, the active drugs had greater efficacy in treating BPSD when compared to placebo. There was no significant difference between the active drugs in terms of tolerability. However, in 2 of the 5 studies, about a third of the patients were noted to have dropped out of the studies. Available data, although limited, do not support the routine use of benzodiazepines for the treatment of BPSD. But these drugs may be used in certain circumstances where other psychotropic medications are unsafe for use in individuals with BPSD or when there are significant medication allergies or tolerability issues with certain classes of psychotropic medications.
Topics: Behavioral Symptoms; Benzodiazepines; Dementia; Humans; Neuropsychological Tests; Patient Dropouts; Psychotropic Drugs; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25551131
DOI: 10.1177/1533317514524813 -
The Cochrane Database of Systematic... Jan 2012Pain management is a high priority for patients with rheumatoid arthritis (RA). Muscle relaxants include drugs that reduce muscle spasm (for example benzodiazepines such... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pain management is a high priority for patients with rheumatoid arthritis (RA). Muscle relaxants include drugs that reduce muscle spasm (for example benzodiazepines such as diazepam (Valium), alprazolam (Xanax), lorazepam (Ativan) and non-benzodiazepines such as metaxalone (Skelaxin) or a combination of paracetamol and orphenadrine (Muscol)) and drugs that prevent increased muscle tone (baclofen and dantrolene). Despite a paucity of evidence supporting their use, antispasmodic and antispasticity muscle relaxants have gained widespread clinical acceptance as adjuvants in the management of patients with chronic musculoskeletal pain.
OBJECTIVES
The aim of this review was to determine the efficacy and safety of muscle relaxants in pain management in patients with RA. The muscle relaxants that were included in this review are the antispasmodic benzodiazepines (alprazolam, bromazepam, chlordiazepoxide,cinolazepam, clonazepam, cloxazolam, clorazepate, diazepam, estazolam, flunitrazepam, flurazepam, flutoprazepam, halazepam, ketazolam, loprazolam, lorazepam, lormetazepam, medazepam, midazolam, nimetazepam, nitrazepam, nordazepam, oxazepam, pinazepam, prazepam, quazepam, temazepam, tetrazepam, triazolam), antispasmodic non-benzodiazepines (cyclobenzaprine, carisoprodol, chlorzoxazone, meprobamate, methocarbamol, metaxalone, orphenadrine, tizanidine and zopiclone), and antispasticity drugs (baclofen and dantrolene sodium).
SEARCH METHODS
We performed a search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 4th quarter 2010), MEDLINE (1950 to week 1 November 2010), EMBASE (Week 44 2010), and PsycINFO (1806 to week 2 November 2010). We also searched the 2008 to 2009 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) abstracts and performed a handsearch of reference lists of relevant articles.
SELECTION CRITERIA
We included randomised controlled trials which compared a muscle relaxant to another therapy (active, including non-pharmacological therapies, or placebo) in adult patients with RA and that reported at least one clinically relevant outcome.
DATA COLLECTION AND ANALYSIS
Two blinded review authors independently extracted data and assessed the risk of bias in the trials. Meta-analyses were used to examine the efficacy of muscle relaxants on pain, depression, sleep and function, as well as their safety.
MAIN RESULTS
Six trials (126 participants) were included in this review. All trials were rated at high risk of bias. Five cross-over trials evaluated a benzodiazepine, four assessed diazepam (n = 71) and one assessed triazolam (n = 15). The sixth trial assessed zopiclone (a non-benzodiazepine) (n = 40) and was a parallel group study. No trial duration was longer than two weeks while three single dose trials assessed outcomes at 24 hours only. Overall the included trials failed to find evidence of a beneficial effect of muscle relaxants over placebo, alone (at 24 hrs, 1 or 2 weeks) or in addition to non-steroidal anti-inflammatory drugs (NSAIDs) (at 24 hrs), on pain intensity, function, or quality of life. Data from two trials of longer than 24 hours duration (n = 74) (diazepam and zopiclone) found that participants who received a muscle relaxant had significantly more adverse events compared with those who received placebo (number needed to harm (NNTH) 3, 95% CI 2 to 7). These were predominantly central nervous system side effects, including dizziness and drowsiness (NNTH 3, 95% CI 2 to 11).
AUTHORS' CONCLUSIONS
Based upon the currently available evidence in patients with RA, benzodiazepines (diazepam and triazolam) do not appear to be beneficial in improving pain over 24 hours or one week. The non-benzodiazepine agent zopiclone also did not significantly reduce pain over two weeks. However, even short term muscle relaxant use (24 hours to 2 weeks) is associated with significant adverse events, predominantly drowsiness and dizziness.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Arthritis, Rheumatoid; Azabicyclo Compounds; Diazepam; Humans; Indomethacin; Muscle Relaxants, Central; Pain Management; Piperazines; Randomized Controlled Trials as Topic; Sulindac; Triazolam
PubMed: 22258993
DOI: 10.1002/14651858.CD008922.pub2 -
The Cochrane Database of Systematic... Mar 2010Alcohol abuse and dependence represents a most serious health problem worldwide with major social, interpersonal and legal interpolations. Besides benzodiazepines,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alcohol abuse and dependence represents a most serious health problem worldwide with major social, interpersonal and legal interpolations. Besides benzodiazepines, anticonvulsants are often used for the treatment of alcohol withdrawal symptoms. Anticonvulsants drugs are indicated for the treatment of alcohol withdrawal syndrome, alone or in combination with benzodiazepine treatments. In spite of the wide use, the exact role of the anticonvulsants for the treatment of alcohol withdrawal has not yet bee adequately assessed.
OBJECTIVES
To evaluate the effectiveness and safety of anticonvulsants in the treatment of alcohol withdrawal.
SEARCH STRATEGY
We searched Cochrane Drugs and Alcohol Group' Register of Trials (December 2009), PubMed, EMBASE, CINAHL (1966 to December 2009), EconLIT (1969 to December 2009). Parallel searches on web sites of health technology assessment and related agencies, and their databases.
SELECTION CRITERIA
Randomized controlled trials (RCTs) examining the effectiveness, safety and overall risk-benefit of anticonvulsants in comparison with a placebo or other pharmacological treatment. All patients were included regardless of age, gender, nationality, and outpatient or inpatient therapy.
DATA COLLECTION AND ANALYSIS
Two authors independently screened and extracted data from studies.
MAIN RESULTS
Fifty-six studies, with a total of 4076 participants, met the inclusion criteria. Comparing anticonvulsants with placebo, no statistically significant differences for the six outcomes considered.Comparing anticonvulsant versus other drug, 19 outcomes considered, results favour anticonvulsants only in the comparison carbamazepine versus benzodiazepine (oxazepam and lorazepam) for alcohol withdrawal symptoms (CIWA-Ar score): 3 studies, 262 participants, MD -1.04 (-1.89 to -0.20), none of the other comparisons reached statistical significance.Comparing different anticonvulsants no statistically significant differences in the two outcomes considered.Comparing anticonvulsants plus other drugs versus other drugs (3 outcomes considered), results from one study, 72 participants, favour paraldehyde plus chloral hydrate versus chlordiazepoxide, for the severe-life threatening side effects, RR 0.12 (0.03 to 0.44).
AUTHORS' CONCLUSIONS
Results of this review do not provide sufficient evidence in favour of anticonvulsants for the treatment of AWS. There are some suggestions that carbamazepine may actually be more effective in treating some aspects of alcohol withdrawal when compared to benzodiazepines, the current first-line regimen for alcohol withdrawal syndrome. Anticonvulsants seem to have limited side effects, although adverse effects are not rigorously reported in the analysed trials.
Topics: Alcohol Withdrawal Delirium; Alcohol Withdrawal Seizures; Anticonvulsants; Humans; Randomized Controlled Trials as Topic
PubMed: 20238337
DOI: 10.1002/14651858.CD005064.pub3 -
The Cochrane Database of Systematic... Apr 2006Managed withdrawal is a necessary step prior to drug-free treatment. It may also represent the end point of maintenance treatment. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Managed withdrawal is a necessary step prior to drug-free treatment. It may also represent the end point of maintenance treatment.
OBJECTIVES
To assess the effectiveness of interventions involving the use of buprenorphine to manage opioid withdrawal, for withdrawal signs and symptoms, completion of withdrawal and adverse effects.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, including the Cochrane Drugs and Alcohol Group trials register, Issue 3, 2005), MEDLINE (January 1966 to August 2005), EMBASE (January 1985 to August 2005), PsycINFO (1967 to August 2005), CINAHL(1982 to July 2005) and reference lists of articles.
SELECTION CRITERIA
Experimental interventions involved the use of buprenorphine to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Comparison interventions involved reducing doses of methadone, alpha2 adrenergic agonists, symptomatic medications or placebo, or different buprenorphine-based regimes.
DATA COLLECTION AND ANALYSIS
One reviewer assessed studies for inclusion and methodological quality, and undertook data extraction. Inclusion decisions and the overall process was confirmed by consultation between all three reviewers.
MAIN RESULTS
Eighteen studies (14 randomised controlled trials), involving 1356 participants, were included. Ten studies compared buprenorphine with clonidine; four compared buprenorphine with methadone; one compared buprenorphine with oxazepam; three compared different rates of buprenorphine dose reduction; two compared different starting doses of buprenorphine. (Two studies included more than one comparison.)Relative to clonidine, buprenorphine is more effective in ameliorating the symptoms of withdrawal, patients treated with buprenorphine stay in treatment for longer, particularly in an outpatient setting (SMD 0.82, 95% CI 0.57 to 1.06, P < 0.001), and are more likely to complete withdrawal treatment (RR 1.73, 95% CI 1.21 to 2.47, P = 0.003). At the same time there is no significant difference in the incidence of adverse effects, but drop-out due to adverse effects may be more likely with clonidine. Severity of withdrawal is similar for withdrawal managed with buprenorphine and withdrawal managed with methadone, but withdrawal symptoms may resolve more quickly with buprenorphine. There is a trend towards completion of withdrawal treatment being more likely with buprenorphine relative to methadone (RR 1.30, 95% CI 0.97 to 1.73, P = 0.08).
AUTHORS' CONCLUSIONS
Buprenorphine is more effective than clonidine for the management of opioid withdrawal. There appears to be no significant difference between buprenorphine and methadone in terms of completion of treatment, but withdrawal symptoms may resolve more quickly with buprenorphine.
Topics: Acute Disease; Buprenorphine; Clonidine; Humans; Narcotic Antagonists; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome
PubMed: 16625553
DOI: 10.1002/14651858.CD002025.pub3 -
The Cochrane Database of Systematic... Oct 2004Managed withdrawal (detoxification) is a necessary step prior to drug-free treatment. It may also represent the end point of long-term opioid replacement treatment such... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Managed withdrawal (detoxification) is a necessary step prior to drug-free treatment. It may also represent the end point of long-term opioid replacement treatment such as methadone maintenance. The availability of managed withdrawal is essential to an effective treatment system.
OBJECTIVES
To assess the effectiveness of interventions involving the use of buprenorphine to manage opioid withdrawal, in terms of withdrawal signs and symptoms, completion of withdrawal and adverse effects.
SEARCH STRATEGY
Multiple electronic databases (including Medline, Embase, PsycINFO, Australian Medical Index, Cochrane Clinical Trials Register) were systematically searched to October 2003. Reference lists of retrieved studies, reviews and conference abstracts were handsearched.
SELECTION CRITERIA
Controlled trials comparing buprenorphine with reducing doses of methadone, alpha2 adrenergic agonists, symptomatic medications or placebo, or comparing different buprenorphine-based regimes, to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent.
DATA COLLECTION AND ANALYSIS
One reviewer assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all three reviewers. Included studies were assessed for methodological quality. Meta-analysis was undertaken where possible, with sensitivity analyses used to assess the impact of methodological quality.
MAIN RESULTS
Thirteen studies (10 RCTs), involving 744 participants, met the criteria for inclusion in the review. Seven studies compared buprenorphine with clonidine; 3 compared buprenorphine with methadone; 1 compared buprenorphine with oxazepam; 2 compared rapid and slow rates of tapering buprenorphine dose; 1 compared 3 different starting doses of buprenorphine. For groups treated with buprenorphine, withdrawal severity was less than that in groups treated with clonidine; peak severity was similar to those treated with methadone, but withdrawal symptoms may resolve more quickly with buprenorphine. Withdrawal is probably more severe when doses are tapered rapidly following a period of maintenance treatment. Buprenorphine is associated with fewer adverse effects than clonidine, and completion of withdrawal is significantly more likely with buprenorphine (Relative Risk 1.35, 95% confidence interval 1.13, 1.62). In the two available studies, there was no statistically significant difference in rates of completion of withdrawal for buprenorphine compared to methadone in reducing doses. Completion of withdrawal following buprenorphine maintenance treatment may be more likely when doses are reduced gradually.
REVIEWERS' CONCLUSIONS
Buprenorphine is more effective than clonidine for the management of opioid withdrawal. There appears to be no significant difference between buprenorphine and methadone in terms of completion of withdrawal, but withdrawal symptoms may resolve more quickly with buprenorphine. Many aspects of treatment protocol and relative effectiveness need to be investigated further in order to determine the most effective way of using buprenorphine to manage opioid withdrawal.
Topics: Acute Disease; Buprenorphine; Clonidine; Humans; Narcotic Antagonists; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome
PubMed: 15495026
DOI: 10.1002/14651858.CD002025.pub2